The purpose of the investigation suggested by the applicant is to study the induction and expression of hypersensitivity in the lung using simple chemicals (haptens). Haptens (2,4,6 Trinitro-1-Chlorobenzene, TNCB; Dinitrofluorobenzene, DNFB) used in the study are similar to chemicals (trimellitic anhydride, TMA) recently described as industrial hazards for workers in the plastics industry. The studies are directed toward the development of an experimental model for pulmonary interstitial disorders that will have relevance for understanding mechanisms of pulmonary disease caused by industrial or environmental chemicals that react as haptens. Animals will be primed by intratracheal inoculation of TNP and contact hypersensitivity (CH) and will be elicited by skin painting the ear. Ear swelling will be indicative of a response. The role of alveolar macrophages (AMPhi) in the induction of CH will be studied by immunizing with haptenated AMPhi. We will then study the ability of hapten deposited in the lung to elicit a pulmonary hypersensitivity reaction in animals previously immunized via the lung or via the skin. The pulmonary reaction will be studied by histologic examination of tissue sections. Pulmonary immune responses will be studied in the various lymphoid compartments of the lung and systemic immune system by quantitating specific antibody forming cells (AFC) and specific T lumphocytes in both proliferation and cytotoxic cell assays. The interaction of hapten sensitivity and influenza infection in the development of lung disease will be studied. Animals will be infected with influenza virus and then exposed to hapten at various time points thereafter. Many workers exposed to haptens may seasonally be infected with influenza and it would be important to know if influenza infection acts as an adjuvant or suppressive agent in the response to inhaled haptens. The interaction of two agents capable of causing pulmonary damage may lead to a chronic lung condition. The lung lesions as well as the accompanying immune responses to the agents will be studied. The results from these studies will give new insights into immune mechanisms that participate in the etiology of pulmonary interstitial diseases.